Neuropeptide Y (hereinafter referred to as NPY) is a peptide which consists of 36 amino acid residues and was isolated from porcine brain in 1982. NPY is widely distributed in the central nervous system and peripheral tissues of humans and animals.
It has been reported that NPY possesses a stimulating activity of food intake, an anti-seizure activity, a learning-promoting activity, an anti-anxiety activity, an antistress activity, etc. in central nervous system, and it may be pivotally involved in the central nervous system diseases such as depression, Alzheimer-type dementia and Parkinson's disease. NPY is thought to be associated with circulatory disorders, since it induces a contraction of smooth muscles such as blood vessels or cardiac muscles in the peripheral tissues. Furthermore, NPY is also known to be involved in the metabolic diseases such as obesity, diabetes and hormone abnormalities (Non-patent Document 1). Therefore, an NPY receptor antagonist is expected as a medicine for preventing or treating various diseases involved in the NPY receptor like the above.
As to NPY receptor, Y1, Y2, Y3, Y4, Y5, and Y6 subtypes have been identified (Non-patent Document 2). It has been suggested that Y5 receptor is at least involved in the feeding behavior and its antagonist is expected as an anti-obesity agent (Non-patent Document 3).
As a NPY Y5 receptor antagonist, WO2001/2379 (Patent Document 1) disclose compounds having a tricyclic condensed hetero ring, JP2003-137872 (Patent Document 2) discloses substituted 2-cyclohexylyl-4-phenyl-1H-imidazole derivatives, WO97/20823 (Patent Document 3) discloses cyclohexane derivatives connecting aryl via methylenecarbonyl group, WO2004/89919 (Patent Document 4) discloses cyclohexanecarboxamido derivatives having a substituted dihydrobenzoxazolyl or substituted dihydrooxazolopyridy, WO2003/010175 (Patent Document 15) and Bioorganic & Medicinal Chemistry Letters (2002), 12(8), 1171-1175 (Non-patent Document 5) discloses cyclohexanecarboxamido derivatives substituted with hydroxy, WO2006/14482 (Patent Document 5) discloses pyrimidine derivatives connecting cyclohexane via iminomethylene group, WO01/37826 (Patent Document 6) and WO2006/001318 (Patent Document 7) disclose sulphonamide compounds, WO2007/125952 (Patent Document 8) and WO2009/054434 (Patent Document 13) disclose amine derivatives, WO2008/026563 (Patent Document 9) discloses hydrazineamide derivatives, WO2008/026564 (Patent Document 10) discloses urea derivatives, WO2009/131096 (Patent Document 14) discloses compounds having a monocyclic or bicyclic aromatic hetero ring. These compounds differ from the compound of the invention in structure.
Also, compounds having a similar structure to the compound of the present invention are disclosed in WO2003/028641 (Patent Document 11), JP2004-315511 (Patent Document 12), WO2004/072025 (Patent Document 16), WO2009/153720 (Patent Document 17), WO2009/106531 (Patent Document 18), WO2006/004040 (Patent Document 19), WO2005/080399 (Patent Document 20), WO2005/063734 (Patent Document 21), JP2005-120080 (Patent Document 22), WO2003/082847 (Patent Document 23), WO98/22432 (Patent Document 24), JP6-271762 (Patent Document 25), JP6-220269 (Patent Document 26), etc. However, these documents do not describe NPY Y5 receptor antagonism to suggest the present invention.    [Patent Document 1] WO2001/2379    [Patent Document 2] JP2003-137872    [Patent Document 3] WO97/20823    [Patent Document 4] WO2004/89919    [Patent Document 5] WO2006/14482    [Patent Document 6] WO01/37826    [Patent Document 7] WO2006/001318    [Patent Document 8] WO2007/125952    [Patent Document 9] WO2008/026563    [Patent Document 10] WO2008/026564    [Patent Document 11] WO2003/028641    [Patent Document 12] JP2004-315511    [Patent Document 13] WO2009/054434    [Patent Document 14] WO2009/131096    [Patent Document 15] WO2003/010175    [Patent Document 16] WO2004/072025    [Patent Document 17] WO2009/153720    [Patent Document 18] WO2009/106531    [Patent Document 19] WO2006/004040    [Patent Document 20] WO2005/080399    [Patent Document 21] WO2005/063734    [Patent Document 22] JP2005-120080    [Patent Document 23] WO2003/082847    [Patent Document 24] WO98/22432    [Patent Document 25] JP6-271762    [Patent Document 26] JP6-220269    [Non-patent Document 1] Trends in Pharmacological Sciences, Vol. 15, 153 (1994)    [Non-patent Document 2] Trends in Pharmacological Sciences, Vol. 18, 372 (1997)    [Non-patent Document 3] Peptides, Vol. 18, 445 (1997)    [Non-patent Document 4] Journal of Medicinal Chemistry (1999), 42(5), 910-919    [Non-patent Document 5] Bioorganic & Medicinal Chemistry Letters (2002), 12(8), 1171-1175